3HK0

Crystal Structure of the RA and PH Domains of Grb10

Summary for 3HK0

• Entry DOI: 10.2210/pdb3hk0/pdb
• Descriptor: Growth factor receptor-bound protein 10, THIOCYANATE ION (3 entities in total)
• Functional Keywords: grb10, ra, ph, ras-associating, pleckstrin-homology, adapter protein, phosphoprotein, sh2 domain, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm (By similarity): Q13322
• Total number of polymer chains: 2
• Total formula weight: 59059.48

Authors

Hubbard, S.R.,Depetris, R.S.,Wu, J. (deposition date: 2009-05-22, release date: 2009-08-04, Last modification date: 2024-02-21)

Primary citation

Depetris, R.S.,Wu, J.,Hubbard, S.R.
Structural and functional studies of the Ras-associating and pleckstrin-homology domains of Grb10 and Grb14.
Nat.Struct.Mol.Biol., 16:833-839, 2009

PubMed Abstract: Growth factor receptor-binding proteins Grb7, Grb10 and Grb14 are adaptor proteins containing a Ras-associating (RA) domain, a pleckstrin-homology (PH) domain, a family-specific BPS (between PH and SH2) region and a C-terminal Src-homology-2 domain. Previous structural studies showed that the Grb14 BPS region binds as a pseudosubstrate inhibitor in the tyrosine kinase domain of the insulin receptor to suppress insulin signaling. Here we report the crystal structure of the RA and PH domains of Grb10 at 2.6-A resolution. The structure reveals that these two domains, along with the intervening linker, form an integrated, dimeric structural unit. Biochemical studies demonstrated that Grb14 binds to activated Ras, which may serve as a timing mechanism for downregulation of insulin signaling. Our results illuminate the membrane-recruitment mechanisms not only of Grb7, Grb10 and Grb14 but also of MIG-10, Rap1-interacting adaptor molecule, lamellipodin and Pico, proteins involved in actin-cytoskeleton rearrangement that share a structurally related RA-PH tandem unit.

PubMed: 19648926
DOI: 10.1038/nsmb.1642

Experimental method

X-RAY DIFFRACTION (2.6 Å)